1. Field of the Invention
The invention relates to the regulation of melanin synthesis. More specifically, the invention is concerned with compositions and methods which modify the activity of tyrosinase.
2. Description of the Prior Art
Pigmentation of human skin and hair is a concern for people around in the world. In some cases the desire is to have an overall lighter complexion. Most generally people wish to have even skin tone regardless of the underlying color. All people wish to delay the appearance of grey hair, which is a sign of aging.
Pigmentation of skin and hair is controlled by the specialized cell called a melanocyte. The melanocyte contains within it an organelle called a melanosome which manufactures the forms of melanin (including black eumelanin and red pheomelanin) and then the melanocyte distributes it within the skin or hair. The most important enzyme in the biosynthesis of melanin is tyrosinase, and its inhibition has been the focus of most commercial products that are designed to lighten skin color.
Tyrosinase is a metalloprotein that is synthesized at ribosomes, trafficked through the Golgi apparatus to a pre-melanosome, and then loaded into it. As the pre-melanosome matures, copper molecules are also loaded into it as co-factors for the tyrosinase, and the pH is increased to reach the optimum for the enzyme. The mature melanosome then begins synthesizing melanin.
The trafficking of tyrosinase is not well understood. Recently, palmitoylation of proteins has received attention as a mechanism of subcellular localization of mammalian proteins (reviewed in T. Iwanaga, R. Tsutsumi, J. Noritake, Y. Fukata, M. Fukata “Dynamic protein palmitoylation in cellular signaling, Progress in Lipid Research 48:117-127, 2009; C. Salaun, J. Greaves, L. Chamberlain “The intracellular dynamic of protein palmitoylation” J. Cell Biol. 191:1229-1238, 2010; C. Aicart-Ramos, R. Valero, I. Rodrigues-Crespo “Protein palmitoylation and subcellular trafficking” Bioch. Biophys. Acta 1808:2981-2994. 2011). Tyrosinase is not disclosed as a target of palmitoylation in any of these reviews.